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AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.
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ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill （SQTLP） on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus （T2DM） mice based on nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） pathway. MethodA total of 60 7-week-old male db/db mice ［specific pathogen-free （SPF） grade］ were selected and fed for one week for adaption. They were divided into the model control group， SQTLP low-， medium- and high-dose （19， 38， and 76 g·kg-1） groups and metformin group （0.26 g·kg-1） by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose （FBG） was detected. Fasting serum insulin （FINS） levels were detected by enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment-insulin resistance （HOMA-IR） index and the homeostasis model assessment-insulin sensitivity index （HOMA-ISI） were calculated. Oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were conducted. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） and the contents of malondialdehyde （MDA） and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species （ROS） and 4-hydroxynonenal （4-HNE） in skeletal muscle tissue were detected by immunofluorescence （IF）. The expression levels of Nrf2， HO-1， NQO1 and glutamate-cysteine ligase catalytic subunit （GCLC） proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group， FBG， FINS and HOMA-IR in the model group were significantly increased （P<0.05）， while HOMA-ISI was decreased （P<0.05）. The results of OGTT and ITT showed that blood glucose was significantly increased at all time points （P<0.05）， and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased （P<0.05）， and MDA and NADPH contents were significantly increased （P<0.05）. In skeletal muscle tissues， the arrangement of muscle fibers was loose， the nucleus was disordered， and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly decreased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the metformin group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points （P<0.05）. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly increased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased （P<0.05）， and the NADPH content was decreased （P<0.05）. The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05）. Compared with those in the SQTLP low-dose group， FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05） in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice， and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway， promoting the expression of antioxidant enzymes， and thus improving the oxidative stress injury in the skeletal muscle.
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Objective Both right and left ventricular function should be taken into account in the assessment of anthracycline (ATC)-induced cardiotoxicity.The aim of this study was to assess the subclinical dysfunction of right cardiac system in patients with newly diagnosed lymphoma who received ATC treatment by echocardiography.Methods A total of 74 patients with lymphoma who received ATC treatment were enrolled.Each patient underwent transthoracic echocardiographic examination before chemotherapy as well as after two,four and six cycles of ATC remedy.Right atrial (RA) and right ventricular (RV) end-diastolic area (EDA) and end-systolic area (ESA) were calculated.RV end-diastolic volume (EDV) and end-systolic volume (ESV),as well as RV ejection fraction (EF) were measured simultaneously.Tissue Doppler imaging (TDI) measurements of systolic and early or late diastolic myocardial velocities of RV free wall at tricuspid annuals were also analyzed.Two-dimensional speckle tracking echocardiography (2DSTE) was conducted to evaluate RV free wall strain along with strain rate.Results None of the echocardiographic parameters showed significant alteration after two and four cycles of chemotherapy compared with those at baseline (P＞0.05).At the end of the therapy (i.e.after six cycles of ATC treatment),there was still no statistical difference on TDI data aswell as 2DSTE measurements (P＞0.05).An unexpected finding was that the RAEDA((6.6±1.9) cm2 vs (7.7±2.4) cm2) and RAESA ((8.8±2.5) cm2 vs (10.8±2.8) cm2) revealed obvious dilatation after six cures of the regimen compared with those at baseline (P＜0.01).Similar morphologic characteristics displayed on the RVEDA ((14.1 ±3.4) cm2 vs (16.2±3.7) cm2) and RVESA ((7.9±1.9) cm2 vs (9.0±2.2) cm2) (P＜0.01)simultaneously.Furthermore,RVEDV ((29.8±10.5) ml vs (37.0±12.7) ml) and RVESV ((12.7±4.4) ml vs (15.0±5.2) ml),as well as RVEF ((59.4±5.8)％ vs (56.4±5.8)％),in patients with lymphoma presented statistically significant difference between basic state and the level after six cycles of chemotherapy (P＜0.01).Meanwhile,no marked change was detected on left ventricular ejection fraction(LVEF) throughout the follow-up period (P＞0.05).Conclusions Echocardiography can be used easily and noninvasively to assess right cardiac system subclinical dysfunction.ATC-induced cardiotoxicity of right cardiac system is firstly manifested as morphological changes than the measurements with novel echocardiographic techniques.In addition,RVEF expresses as a valuable parameter for assessing subtle RV impaired performance in patients with lymphoma received ATC therapy.
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Objective To evaluate the subclinical dysfunction of left ventricle (LV) induced by anthracycline(ATC) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) by two-dimensional speckle tracking echocardiography (2DSTE) as well as real-time three-dimensional echocardiography (RT3DE).Methods Traditional echocardiography images and RT3DE images were acquired from 59 patients with DLBCL before,after the completion of two cures(100 mg∕m 2)and four cures of the regimen(200 mg∕m 2).LV global longitudinal strain(GLS),global circumferential strain(GCS),LV apical rotation and basal rotation,LV end-diastolic volume (EDV),end-systolic volume (ESV),stroke volume(SV) and ejection fraction(EF)were calculated simultaneously.Results Compared with baseline, LV apical rotation and basal rotation reduced significantly after two cures and four cures of therapy [LV apical rotation:(5.34±1 .80)°vs (3.80±1 .45)°vs (2.96±1 .1 8)°;LV basal rotation:(-3.32±1 .14)°vs (-2.65±1 .12)°vs (-2.56±1 .19)°;both P 0.05 for all). Conclusions Cardiotoxicity during the early phase of anthracycline treatment can be detected via 2DSTE prior to the traditional echocardiographic expression of ventricular systolic function.The left ventricular rotation index seems to be more sensitive than strain parameters for the estimation of early cardiac injury in patients with ATC chemotherapy.There is no safe dose for anthracycline in all patients with DLBCL treated with anthracycline even at lower doses.
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ObjectiveTo determine the serum vitamin D levels of patients with primary hypertension to provide a basis for prevention and control of the hypertension in Kashgar prefecture.Methods The clinical data of 200 patients with hypertension in Kashgar prefecture admitted to the Second People's Hospital from January 2014 to December 2015 were retrospectively analyzed. According to risk factors, the 200 patients with primary hypertension were divided into three groups: 60 patients were selected as low risk group (hypertension 1 grade and no risk factors), 64 patients were arranged into an intermediate risk group (hypertension 2 grade or hypertension 1 grade accompanied by 1-2 risk factors) and 76 patients were assigned in a high risk group (hypertension 3 grade or hypertension 1-2 grade accompanied by ≥3 risk factors or hypertension of any grade accompanied by 1 target organ damage or 1 kind of clinical disease). In the same period, 66 healthy subjects having taken physical systemic medical examination with normal blood pressure in this hospital were grouped into a healthy control group. The levels of blood pressure and vitamin D in serum were measured, and the correlations between vitamin D and systolic blood pressure (SBP), diastolic blood pressure (DBP) were analyzed by pearson correlation analysis in the four groups.Results The SBP and DBP were significantly higher in low, intermediate and high risk group than those in healthy control group [SBP (mmHg, 1 mmHg = 0.133 kPa): 142±6, 161±5, 173±12 vs. 112±12, DBP (mmHg): 89±7, 101±4, 103±11 vs. 74±8], and their levels of vitamin D were lower in low, intermediate, high risk group than the level in healthy control group (μg/L: 24±6, 26±5, 20±4 vs. 30±7, allP < 0.05). Correlation analysis showed that the level of vitamin D was negatively correlated with SBP, DBP (r value was -0.373, -0.324, allP < 0.01).Conclusions The serum level of vitamin D is decreased in Uighur patients with blood hypertension in Kashgar prefecture, especially in the patients with high risk factors, the descent of the serum level is more significant. It is suggested to appropriately use vitamin D supplement to prevent blood hypertension.
